Deletion of wheat alpha-gliadins from chromosome 6D improves gluten strength and reduces immunodominant celiac disease epitopes

Authors: ROTTERSMAN, MARIA - University Of California; ZHANG, WENJUN - University Of California; ZHANG, JUNLI - University Of California; GRIGORIAN, GABRIELA - University Of California; BURGUENER, GERMAN - Howard Hughes Medical Institute; CARTER, CLAUDIA - California Wheat Commission; VANG, TENG - California Wheat Commission; HEGARTY, JOSHUA - University Of California; ZHANG, XIAOQIN - University Of California; Finnie, Sean; DUBCOVSKY, JORGE - University Of California

Submitted to: Theoretical and Applied Genetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/11/2025
Publication Date: 4/9/2025
Citation: Rottersman, M.G., Zhang, W., Zhang, J., Grigorian, G., Burguener, G., Carter, C., Vang, T., Hegarty, J., Zhang, X., Finnie, S.M., Dubcovsky, J. 2025. Deletion of wheat alpha-gliadins from chromosome 6D improves gluten strength and reduces immunodominant celiac disease epitopes. Theoretical and Applied Genetics. 2025(138). Article 94. https://doi.org/10.1007/s00122-025-04882-3.
DOI: https://doi.org/10.1007/s00122-025-04882-3

Interpretive Summary: Celiac disease (CeD), a common immune-mediated condition characterized by inflammation of the small intestine, affects approximately 1% of the world’s population, and its incidence has been increasing over time. CeD is triggered in genetically predisposed individuals by long term consumption of wheat gluten and gluten-like peptides. Currently the only effective treatment for CeD is a completely gluten-free diet. However, even those who strictly adhere to a gluten-free diet may suffer from compromised health due to nutritional imbalance and a less robust gut microbiome, social isolation, and an increased cost of living. In this study, we characterize the size of the deletions and their effect on grain yield, grain protein content and breadmaking quality. Finally, we present proteomic results that explain the beneficial effects of the gli-D2 deletion on breadmaking quality relative to deletions.

Technical Abstract: Wheat gliadins and glutenins confer valuable end-use characteristics but include amino acid sequences (epitopes) that can elicit celiac disease (CeD) in genetically predisposed individuals. The onset of CeD in these individuals is affected by the amount and duration of the exposure to immunogenic epitopes. Therefore, a reduction of epitopes that result in high immune responses in the majority of CeD patients (immunodominant epitopes) may reduce the incidence of CeD at a population level. We generated gamma radiation-induced deletions encompassing the '-gliadins at the three wheat genomes and characterized them using exome capture. These deletions, designated as 'gli-A2, 'gli-B2, and 'gli-D2, were deposited in GRIN-Global. The 'gli-A2 and 'gli-B2 deletions showed limited effects on breadmaking quality, but the 'gli-D2 deletion significantly increased gluten strength and improved breadmaking quality without compromising dough elasticity, protein content or grain yield. The stronger effect of 'gli-D2 on gluten strength was associated with an increased proportion of glutenins and the deletion of '-gliadins with seven cysteines, which are absent in the GLI-A2 and GLI-B2 loci. We show that '-gliadins with seven cysteines are incorporated into the gluten polymer, where they likely function as chain-terminators limiting the expansion of the gluten polymer and reducing its strength. In addition to its beneficial effects on breadmaking quality, the 'gli-D2 deletion eliminates major wheat immunodominant CeD epitopes. The deployment of this publicly available 'gli-D2 deletion can simultaneously improve wheat gluten strength and reduce immunodominant CeD epitopes, which has the potential to reduce the population-wide burden of CeD.